Features

• 2 major phenotypes
  • Typical CF: chronic sinopulmonary infection, nasal polyps (10-32%), hepatobiliary disease, pancreatic insufficiency, meconeum ileus at birth, elevated sweat chloride values, obstructive azoospermia
  • Atypical CF: as above, except sweat chloride is normal or borderline, and there is no meconeum ileus, pancreatic insufficiency, hepatobiliary disease
• Lung disease may be complicated by ABPA
• Frequency
  • 50% of children (4-16 years old) presenting with nasal polyps have CF
  • 1 in 2,500–3,500 Caucasian Americans
  • 1 in 4,000–10,000 Hispanic Americans
  • 1 in 15,000–20,000 African Americans
  • 1 in 100,000 Asian Americans

Diagnosis

• AR mutation in CFTR chloride channel gene (>1000 mutations identified), affecting 1/3700 births, most common in (but not restricted to) Caucasians
• Diagnostic criteria:

• Newborn screen tests for immunoreactve trypsinogen (IRT) level which is 2-5 times higher in CF due to leakage of pancreatic secretions into the circulation caused by blocked pancreatic ducts
  • If IRT abnormal, some states confirm with repeat IRT, others perform DNA test

• Sweat chloride test (quantitative pilocarpine iontophoresis) - diagnostic gold standard if done at an accredited CF center
  • Results
    • <40 mmol/L - negative
    • 40-60 mmol/L = borderline (infants <6 months can have lower values, therefore 30-60 considered borderline)
    • >60 mmol/L - positive
    • Note that some mutations (atypical CF) are associated with normal sweat test (~1% with CF have normal sweat chloride)
  • Diseases other than CF with elevated sweat chloride:
    • Adrenal insufficiency
    • Pseudohypoaldosteronism
    • Hypothyroidism
    • Hypoparathyroidism
    • Nephrogenic diabetes insipidus
    • Ectodermal dysplasia
    • Glycogen storage disease (type I)
    • Mucopolysaccharidoses
    • Fucosidosis
    • Malnutrition
    • Mauriac syndrome
    • Familial cholestasis syndrome
    • Pancreatitis
    • Prostaglandin E1 administration
    • Hypogammaglobulinemia

• CFTR DNA mutatation analysis - confirms diagnosis if 2 CF-related mutations are found
  • F508 mutation accounts for 70% in Caucasians (30-48% in other groups), with 15-20 other common mutations accounting for 2-15%
  • Initial screen (e.g. Quest Diagnostics "CF screen") includes 23 (basic) to 32 (extended) of the most common CF mutations, and will detect CF in 90% of Caucasians and 97% of Ashkenazi Jews (lower in other ethnic groups)
  • If CF screen detects 0-1 mutations, consider expanded DNA analysis (e.g. Quest Diagnostics "CF Complete") via CFTR gene sequencing
    
    

    Quest Diagnostics CF Test Selection Guide.pdf
    

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Algorithm (Katkin)

CF and ABPA